BEES-HAUS preventing urethral stricture recurrence by restoring the integrity of urothelium and its further simplified version, the BHES-HAUS

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Urethral stricture disease (USD) is a persistent, distressing condition that leads to considerable urinary difficulties and sexual complications [1]. Urethral stricture is the narrowing of the urethral lumen caused by fibrotic changes arising from congenital or acquired pathological conditions, with an estimated prevalence of about 0.6%. USD denotes the progressive scarring process that involves the urethral epithelium or the spongy erectile tissue of the corpus spongiosum (spongiofibrosis) [2]. While USD may remain asymptomatic in its early stages, progressive narrowing of the lumen eventually leads to significant voiding difficulties. The causes of urethral strictures are broadly categorized into five groups: idiopathic, iatrogenic, infections, inflammatory, and traumatic [3]. Among these, idiopathic and iatrogenic etiologies are the most frequent, each contributing to approximately one-third of cases. Traumatic origins account for about 19%, while inflammatory causes make up around 15% [3].The pathophysiology of urethral stricture disease is primarily driven by fibrosis. Evidence suggests that patients with strictures exhibit alterations in the extracellular matrix (ECM) glycosaminoglycan profile compared to healthy individuals, with reduced hyaluronic acid and increased dermatan sulfate concentrations. These findings indicate that stricture segments represent a later stage of wound healing and point toward prior urethral injury as a key etiological factor. Moreover, chronic inflammation plays a central role, as fibrosis represents the end stage of persistent inflammatory processes and is largely irreversible [4]. Injury to the urethral epithelium either through urine extravasation into the corpus spongiosum or direct trauma triggers inflammation and subsequent fibrotic remodeling of the spongiosum. The accumulation and contraction of fibrotic tissue progressively narrow the urethral lumen.Additionally, epithelial metaplasia to stratified squamous epithelium increases susceptibility to mechanical stress and microtrauma. This heightened vulnerability predisposes to mucosal tears, further urinary leakage, and perpetuation of fibrosis. Consequently, a vicious cycle of epithelial damage, inflammation, and fibrotic remodeling results in progressive urethral narrowing and recurrent stricture formation [4].In the absence of complications, the primary goal of USD management is symptom relief.Treatment decisions are guided by symptom severity, stricture location, length, and patient preference. In healthy young men, the normal peak urinary flow rate (Q-max) is >15 mL/s, whereas most patients with strictures present with reduced flow rates (<12 mL/s). Those with flow rates between 10 and 15 mL/s are often asymptomatic and typically do not require intervention, provided there is no evidence of bladder wall thickening or incomplete emptying.A peak flow rate of 5-10 mL/s, however, is usually associated with obstructive symptoms and potential complications [4]. In cases of acute urinary retention or related complications, urgent interventions include urethral dilation, cystoscopy, direct vision internal urethrotomy (DVIU), or suprapubic cystostomy. Broadly, treatment strategies fall into two categories which are endoscopic approaches such as urethral dilatation and DVIU and open surgical procedures such as stricture excision and anastomotic urethroplasty, substitution urethroplasty and diversion like perineal urethrostomy. Urethral dilatation is performed to gradually widen the narrowed urethra caused by stricture which can be achieved using two main techniques [4], bougie or sound dilatation wherein a series of progressively larger, lubricated rods (bougies or sounds) are gently passed into the urethra to enlarge the lumen and identify sites of obstruction or balloon dilatation where an inflatable balloon catheter is introduced under urethroscopic guidance, usually over a flexible guidewire. Once positioned across the stricture, the balloon is inflated to expand the narrowed segment, providing a less traumatic alternative to traditional dilatation methods [5]. Next is DVIU, the most common first-line option for short (<2 cm) untreated bulbar strictures which involves a transurethral incision at the 12 o'clock position to release the fibrotic segment, allowing secondary healing and lumen expansion. Despite being effective in select patients, recurrence rates remain high, reaching up to 65% within three years.Recent studies suggest adjunctive treatments may improve outcomes. For instance, intralesional botulinum toxin injection administered during DVIU has been shown in a randomized, double-blind trial to enhance prognosis and reduce recurrence [4]. Similarly, paclitaxel-coated balloon dilation combined with DVIU has demonstrated superior results in recurrent bulbar strictures <3 cm compared to DVIU alone [6]. Paclitaxel, widely used in vascular interventions for its anti-inflammatory and anti-proliferative effects, provides localized drug delivery to the strictured segment, inhibiting scar tissue regrowth and markedly lowering recurrence rates [4,6].Urethroplasty is considered as the gold standard for managing urethral stricture and stenosis, with both excisional urethroplasty and graft-based techniques showing superior long-term success compared to other modalities. Excision and primary anastomosis (EPA), which involves removing the fibrotic segment and rejoining the healthy urethral ends, is regarded as the optimal treatment for short bulbar strictures regardless of cause or prior interventions [7].However, a limitation of all the endoscopic procedures is the lack of epithelial coverage, leaving subepithelial tissue exposed to urine, which may promote infection and myofibroblast proliferation leading to fibrosis, thereby contributing to recurrence [8,9]. Avoidance of urine leakage is a critical factor in preventing stricture formation, particularly given the highly cytotoxic nature of urine. In the normal urethra, the barrier function of the urothelium is maintained through three key components: uroplakin proteins within the apical cell membrane, tight junctions between superficial umbrella cells, and a protective layer of glycosaminoglycans (GAGs) and proteoglycans coating the umbrella cell surface. Thus, proper formation and regeneration of the urothelium are essential to maintain this barrier, as disruption can predispose to urethral stricture development. Furthermore, an intact urothelium plays an important role in preventing detrusor muscle overactivity, inflammation, and fibrosis within the urinary tract [8].This drawback of lack of epithelial coverage is addressed in open surgical procedures, where grafts or flaps provide epithelial lining and structural reinforcement, particularly useful for long or anatomically complex strictures such as those in the penile urethra [10]. Historically, penile or scrotal skin flaps were used but had failure rates of 20-30%, while split-thickness skin grafts (STSGs) achieved around 80% success [10] but required multiple stages and carried donor-site morbidity; bladder mucosa has also been used but with moderate failure rates and the disadvantage of invasive harvesting. The introduction of buccal mucosal grafts (BMGs) in the 1990s transformed urethral reconstruction due to their robust, non-keratinized stratified squamous epithelium, similarity to urethral tissue, resistance to infection, thick elastic epithelium, thin lamina propria, and abundant availability with minimal donor-site morbidity [11]. However, the use of buccal mucosal grafts is not without limitations, as the restricted availability of autologous tissue and donor site morbidity remain significant clinical challenges.Patients undergoing buccal tissue harvest may develop scarring, contracture, persistent pain, numbness, or parotid duct injury, with reported oral complication rates ranging from 3% to 4% [8]. Moreover, buccal mucosa urethroplasty is general

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